Cardiac glycosides are the main pharmacoloic tools in the treatment of congestive heart failure. However, the toxic to safety does ratio is low often no more than two or three to one. This difficulty is further exaccerbated by the marked sensitivity of the therapeutic and toxic doses to changes in plasma ion concentrations. A major aim of this poject is to investigate the interactions of plasma ions with cardiac muscle in the presence and absence of uncover the mechanism of their interaction. A second aim of the project is to pursue the preliminary finding that salicylate can reverse the electrophysiologic manifestations of glycoside toxicity. These experiments may provide a means of preventing or reversing cardiac glycoside toxicity.